We are proposing quantum-chemical calculations of the conformational and electronic properties of a series of opiate narcotic analgesics in order to help elucidate, on a more fundamental level than heretofore attempted, the molecular requirements for analgesic potency, antagonism and perhaps the concommitent physical dependence capacity. All of these phenomena are admittedly complicated, requiring multidisciplinary effort for elucidation. However, the large amount of empirical and clinical data now available and the correlations with drug characteristics which have been tentatively drawn from them, make our attempt to "go a step further" by the calculation and identification of basic molecular properties which correlate to observed behavior, a possible timely and perhaps useful one. Should we in fact be successful in identification of such properties, this information could help in the future search for non-addictive analygesics and of appropriate drugs in the treatment of addiction. The specific series of opiates we have chosen to study have been carefully selected on the basis of the availability of clinical and experimental data, on interesting variations in observed properties which we hope to explain and for their clinical relevance. They are: (1) A series of oxymorphone N-R derivatives including naloxone, (Project I); (2) A series of recently synthesized 5, 9 N-methyl benzomorphan derivatives including metazocine which are weak antagonist and have low physical dependence capacity, (Project IIA); (3) A series of 2R 5, 9, dimethyl benzomorphan derivatives including phenazocine and pentazocine, (Project IIB); (4) A number of N-methyl C7-R compounds in the extremely potent "M-series" of opiates including etorphine and selected allyl and methyl cyclopropyl derivates; (Project III); (5) Four flexible molecules: methadone, mepiridine, propiram and tilidine to investigate the plausibility that they act at the receptor site in "morphine-like" conformations, (Project IV.)